scholarly journals Human Umbilical Cord-Derived Mesenchymal Stem Cell Therapy Ameliorates Nonalcoholic Fatty Liver Disease in Obese Type 2 Diabetic Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Bing Li ◽  
Yu Cheng ◽  
Songyan Yu ◽  
Li Zang ◽  
Yaqi Yin ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepatic Steatosis ◽  
Umbilical Cord ◽  
Fatty Liver Disease ◽  
Human Umbilical Cord ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is increasingly common among patients with type 2 diabetes mellitus (T2DM). The two conditions can act synergistically to produce adverse outcomes. However, the therapeutic options for patients with NAFLD and T2DM are currently limited. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) have shown therapeutic potential for diabetes and hepatic disorders such as liver cirrhosis and fulminant hepatic failure. The present study is aimed at investigating the effect of human UC-MSCs on a mouse model of NAFLD and T2DM, characterized by obesity-induced hyperglycaemia, dyslipidaemia, hepatic steatosis, and liver dysfunction. Thirty-week-old male C57BL/6 db/db mice were infused with human UC-MSCs or phosphate-buffered saline (PBS) via the tail vein once a week for six weeks. Age-matched male C57BL/6 wild-type db/+ mice were used as controls. Body weight and random blood glucose were measured every week. One week after the sixth infusion, intraperitoneal glucose tolerance tests and insulin tolerance tests were performed and the blood and liver were harvested for biochemical and histopathological examinations. Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR), immunofluorescence staining, and western blot were performed to monitor the expression of the lipid metabolism- and regulatory pathway-related genes. UC-MSC infusions significantly ameliorated hyperglycaemia, attenuated the elevation of hepatic transaminases, and decreased lipid contents, including triglyceride, total cholesterol, and low-density lipoprotein cholesterol. Moreover, histological lesions in the liver diminished markedly, as evidenced by reduced lipid accumulation and attenuated hepatic steatosis. Mechanistically, UC-MSCs were found to regulate lipid metabolism by increasing the expression of fatty acid oxidation-related genes and inhibiting the expression of lipogenesis-related genes, which were associated with the upregulation of the HNF4α-CES2 pathway. Our results demonstrate that human UC-MSCs can ameliorate NAFLD and reverse metabolic syndrome in db/db mice. Thus, UC-MSCs may serve as a novel therapeutic agent for T2DM patients with NAFLD.

Resveratrol protects against nonalcoholic fatty liver disease by improving lipid metabolism and redox homeostasis via the PPARα pathway

2020 ◽  
Vol 45 (3) ◽  
pp. 227-239 ◽  
Author(s):  
Yujie Huang ◽  
Hedong Lang ◽  
Ka Chen ◽  
Yong Zhang ◽  
Yanxiang Gao ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Protein Kinase ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepatic Steatosis ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
Redox Homeostasis ◽  
Nonalcoholic Fatty Liver

Resveratrol (RSV), a well-known bioactive compound, has been reported to exert a broad range of health benefits. Accumulating evidence suggests that RSV is beneficial for many metabolic diseases, including nonalcoholic fatty liver disease (NAFLD). This study investigated the preventive and therapeutic effects of RSV on high-fat diet (HFD)-induced NAFLD in rats and palmitate acid (PA)-induced hepatocyte steatosis in HepG2 cells. Hepatocytes were incubated with inhibitors of peroxisome proliferator-activated receptor α (PPARα) or short interfering RNAs (siRNAs) targeting PPARα, AMP-activated protein kinase (AMPK), and protein kinase A (PKA) to determine the underlying mechanisms. We found that RSV noticeably ameliorated HFD-induced hepatic steatosis in rats and inhibited PA-induced lipid accumulation in HepG2 cells. Moreover, RSV improved lipid metabolism, enhanced antioxidant capacity, and restored mitochondrial respiratory chain activities. Incubation with inhibitors of PPARα or PPARα siRNA abolished the protective effects of RSV on lipid metabolism and redox homeostasis. Furthermore, RSV activated the PKA/AMPK/PPARα signaling pathway. Our results provided direct evidence for a novel, PPARα-mediated mechanism responsible for the beneficial effects of RSV on hepatic steatosis. These findings may have important theoretical and application prospects for the prevention and treatment of NAFLD. Novelty RSV improved lipid metabolism and redox homeostasis and oxidative stress in NAFLD via the PKA/AMPK/PPARα signaling pathway. RSV may have a greater beneficial effect in the early prevention of hepatic steatosis.

scholarly journals Multidisciplinary Pharmacotherapeutic Options for Nonalcoholic Fatty Liver Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Kei Nakajima
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Lipid Lowering ◽  
Nonalcoholic Fatty Liver ◽  
Ras Blockers

Nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are multidisciplinary liver diseases that often accompany type 2 diabetes or metabolic syndrome, which are characterized by insulin resistance. Therefore, effective treatment of type 2 diabetes and metabolic syndrome should target not only the cardiometabolic abnormalities, but also the associated liver disorders. In the last decade, it has been shown that metformin, thiazolidinediones, vitamin E, ezetimibe, n-3 polyunsaturated fatty acids, renin-angiotensin system (RAS) blockers, and antiobesity drugs may improve hepatic pathophysiological disorders as well as clinical parameters. Accordingly, insulin sensitizers, antioxidative agents, Niemann-Pick C1-like 1 (NPC1L1) inhibitors, RAS blockers, and drugs that target the central nervous system may represent candidate pharmacotherapies for NAFLD and possibly NASH. However, the efficacy, safety, and tolerability of long-term treatment (potentially for many years) with these drugs have not been fully established. Furthermore, clinical trials have not comprehensively examined the efficacy of lipid-lowering drugs (i.e., statins, fibrates, and NPC1L1 inhibitors) for the treatment of NAFLD. Although clinical evidence for RAS blockers and incretin-based agents (GLP-1 analogs and dipeptidyl peptidase-4 inhibitors) is also lacking, these agents are promising in terms of their insulin-sensitizing and anti-inflammatory effects without causing weight gain.

scholarly journals Prevalence of clinically relevant liver fibrosis due to nonalcoholic fatty liver disease in Indian individuals with type 2 diabetes

JGH Open ◽  
2021 ◽  
Author(s):  
Mohammad Shafi Kuchay ◽  
Narendra Singh Choudhary ◽  
Sunil Kumar Mishra ◽  
Tarannum Bano ◽  
Sakshi Gagneja ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver
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